Ribozyme uses in retinal gene therapy

In this chapter we discuss the design, delivery and preclinical testing of mutation-specific ribozymes for the treatment of dominantly inherited retin al disease. We focus particular attention on the initial screening of riboz ymes in vitro, because the activity of RNA enzymes in cell-free systems can be used to predict their suitability for animal experiments. Current techn iques for delivering genes of Interest to cells of the retina using viral v ectors are then briefly surveyed emphasizing vector properties that best ma rch to the needs of a ribozyme-based therapy. Using these considerations, a nalysis of ribozyme gene therapy for an autosomal dominant RP-like disease in a rodent model is outlined emphasizing the desirability of combining bio chemical, morphological and electrophysiological measures of therapy. Final ly, we describe alternative. perhaps more general, ribozyme approaches that have yet to be tested in the context of retinal disease. (C) 2000 Publishe d by Elsevier Science Ltd.